Sleep during development: Sex and gender differences.

Sleep occupies a substantial proportion of life. Sleep modifications parallel brain development during childhood. Sex and gender differences have been reported in brain development and many clinical and psychosocial conditions. This narrative review provides insight into the differences between girls and boys in terms of brain maturation and plasticity related to sleep and sleep characteristics (physiology, sleep duration) during development.

The French Sleep Disturbance Scale for Children.

OBJECTIVE: The psychometric properties of the Sleep Disturbance Scale for Children (SDSC) have been shown to be accurate, even when translated into several languages. The aim of the present study was to translate, adapt, and validate the SDSC for a French-speaking population. METHODS: After forward- and back-translation, the tool was further translated and adapted into the French language. It was then pretested in terms of clarity on 33 French-speaking parents. Pretesting demonstrated that the questionnaire was well understood, indicating good clarity. During the validation phase, a total of 447 French-speaking parents of children aged between 4 and 16  years completed the SDSC. Among these, 66 children were diagnosed with sleep disorders by a pediatric specialist after a sleep consultation and polysomnographic recordings. RESULTS: The factor analysis revealed five factors: difficulty in initiating and maintaining sleep (DIMS), sleep breathing disorders (SBD), disorders of excessive somnolence (DOES), parasomnias (PARA) and non-restorative sleep (NRS). This psychometric structure is reliable and logical in comparison with the experts' diagnoses. Convergent validity, divergent and internal reliability are very good. Inter-parental concordance in scoring the child's sleep problem does show differences in the ways in which parents report their children's sleep patterns. Cut-off was calculated for the total score (45). CONCLUSION: This study validated a 25-item French version of the questionnaire. The French SDSC could therefore be used to aid screening of sleep disorders in the general population.

High bicarbonate levels in narcoleptic children.

The objective of this study was to evaluate the levels of plasma bicarbonate levels in narcoleptic children. Clinical, electrophysiological data and bicarbonate levels were evaluated retrospectively in children seen in our paediatric national reference centre for hypersomnia. The cohort included 23 control subjects (11.5 ± 4 years, 43% boys) and 51 patients presenting de-novo narcolepsy (N) (12.7 ± 3.7 years, 47% boys). In narcoleptic children, cataplexy was present in 78% and DQB1*0602 was positive in 96%. The control children were less obese (2 versus 47%, P = 0.001). Compared with control subjects, narcoleptic children had higher bicarbonate levels (P = 0.02) as well as higher PCO2 (P < 0.01) and lower venous pH gas (P < 0.01). Bicarbonate levels higher than 27 mmol L(-1) were found in 41.2% of the narcoleptic children and 4.2% of the controls (P = 0.001). Bicarbonate levels were correlated with the Adapted Epworth Sleepiness Scale (P = 0.01). Narcoleptic patients without obesity often had bicarbonate levels higher than 27 mmol L (-1) (55 versus 25%, P = 0.025). No differences were found between children with and without cataplexy. In conclusion, narcoleptic patients had higher bicarbonate plasma levels compared to control children. This result could be a marker of hypoventilation in this pathology, provoking an increase in PCO2 and therefore a respiratory acidosis, compensated by an increase in plasma bicarbonates. This simple screening tool could be useful for prioritizing children for sleep laboratory evaluation in practice.

Quality of life in children with narcolepsy.

AIMS: To evaluate the health-related quality of life (HRQL) and its correlates in children and adolescents with narcolepsy. METHODS: We compared the clinical characteristics of control subjects and patients with primary narcolepsy from data collected at the National Reference Centers for Narcolepsy. RESULTS: The cohort included 69 control subjects (29 boys) and 117 patients (65 boys; 59 de novo patients). Cataplexy was present in 81% and DQB1*0602 was positive in 91%. The control children were older (13.5±3.2 vs. 11.6±3.1 years, P<0.001) and less obese (1.4% vs. 60%, P<0.001). Twenty-five percent of the patients and 15.6% of the control subjects had clinically significant depressive feelings on Children's Depression Inventory (CDI≥16) (NS). Fifty-three narcoleptic and 43 control adolescents, 31 narcoleptic children and 23 control children filled out the HRQL questionnaires as well as 83 parents of patients and 60 parents of control subjects. Narcolepsy seriously impacts HRQL in terms of vitality, physical well-being, relations with friends and leisure activities, especially in adolescents. Depression was the factor that most affected HRQL in both narcoleptic and control subjects. For the control subjects and the narcoleptic patients, when the CDI score was entered into the multivariable regression model adjusted for gender and age, no other continuous independent variable could significantly increase the likelihood of the model. When the CDI score increased by 1, the mean HRQL score decreased by 1.7 for narcoleptic patients and 1.5 for control subjects. Apnea-hypopnoea index, diagnosis delay, disease duration, obesity, the presence of cataplexy or treatment had no effects on HRQL. CONCLUSIONS: Narcoleptic children and adolescents were at high risk for poor HRQL. Depressive symptoms had a major impact on HRQL. We recommend a more thorough assessment and management of psychological health in this population.

Depressive feelings in children with narcolepsy.

OBJECTIVES: We aimed to evaluate depressive feelings and their correlations in children and adolescents with narcolepsy collected in national reference centers for narcolepsy. METHODS: We compared clinical and sleep characteristics of patients with and without depressive symptoms evaluated on the Children's Depression Inventory (CDI). RESULTS: Our study sample included 88 children (44 boys; 44 de novo patients) with a mean age of 11.9 ± 3.1 years at diagnosis (37.5% were aged ⩽ 10 years). Obesity was found in 59% of the sample and cataplexy was present in 80.7%. The DQB1*0602 allele was positive in 93.5% of our sample. There were 25% of children who had clinically depressive feelings (CDI>16), especially girls older than the age of 10 years. Bivariate associations indicated that depressive feelings were associated with fatigue (48%), hyperactivity (31%), insomnia (16%), and excessive daytime sleepiness (EDS) (14-24%). In the multivariate model adjusted for gender and age, only fatigue explained the variability of the depression score. CONCLUSION: In our large cohort, high levels of depressive symptoms essentially expressed by fatigue affected 25% of children with narcolepsy. The girls older than 10 years of age were especially vulnerable. The similar prevalence of depressive feelings in treated vs never-treated patients suggests a specific need for diagnosing and managing this symptom in young patients with narcolepsy.

Pitolisant, an inverse agonist of the histamine H3 receptor: an alternative stimulant for narcolepsy-cataplexy in teenagers with refractory sleepiness.

OBJECTIVE: Narcolepsy is a rare disabling sleep disorder characterized by excessive daytime sleepiness and cataplexy (sudden loss of muscle tone). Drugs such as pitolisant, which block histamine H3 autoreceptors, constitute a newly identified class of stimulants because they increase brain histamine and enhance wakefulness in animal and human adult narcolepsy. METHODS: We report our experience with the off-label use of pitolisant in 4 teenagers with narcolepsy/cataplexy with severe daytime sleepiness, refractory to available treatments (modafinil, methylphenidate, mazindol, sodium oxybate, and D-amphetamine). RESULTS: All teenagers developed their disease during childhood (11.3 ± 2.4 years; 50% boys) and were 17.3 ± 0.8 years old at the time of pitolisant therapy. Pitolisant treatment was increased from 10 to 30 mg (n = 1) and 40 mg (n = 3). The adapted Epworth Sleepiness Score decreased from 14.3 ± 1.1 to 9.5 ± 2.9 (P = 0.03) with pitolisant alone to 7 ± 3.4 when combined with mazindol (n = 1), methylphenidate (n = 1), or sodium oxybate plus modafinil (n = 1). Mean sleep onset latency increased from 31 ± 14 minutes to 36 ± 8 minutes (P = 0.21) on the maintenance of wakefulness test. The severity and frequency of cataplexy were slightly improved. Adverse effects were minor (insomnia, headache, hot flushes, leg pain, and hallucinations) and transitory, except for insomnia, which persisted in 2 teenagers. The benefit was maintained after a mean of 13 months. CONCLUSIONS: Pitolisant could constitute an acceptable alternative for the treatment of refractory sleepiness in teenagers with narcolepsy.